Abstract
Simple SummaryRenal collecting duct carcinoma (CDC) is rare, but very aggressive, variant histology of kidney cancers. Besides surgery, the other therapeutic options, such as pharmacological or radiation therapy, have a poor impact on survival. Therefore, there is an urgent need to identify novel targets that can open up new avenues for alternative treatments. From this perspective, the aim of our study was to assess the HER2 protein expression by immunohistochemistry (IHC) and the gene copy number by fluorescence in-situ hybridization (FISH) in a cohort of 26 CDC. According to the 2018 ASCO/CAP guidelines, 2/26 CDC cases (8%) were HER2-positive. The HER2 protein is a well-established target of anti-HER2 mAbs or kinase inhibitors already used for breast and gastric cancer treatment. Thus, this study provides evidence that supports future biomarker-driven clinical trials that could address the lack of therapy, which is still an unmet clinical need for CDC patients.Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options. We collected 26 CDC cases, and we assessed HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in-situ hybridization (FISH) according to 2018 ASCO/CAP HER2-testing recommendations. Six out of twenty-six (23%) tumors showed HER2 positive staining. In particular, 3+ score was present in 2/6 cases (33%), 2+ in 3/6 cases (50%) and 1+ in 1/6 cases (17%). The 6 HER2+ tumors were also analyzed by FISH to assess gene copy number. One out of six CDC with IHC 3+ was also HER2 amplified, showing an average HER2 copy number ≥4.0 (10.85) and a HER2/CEP17 ratio ≥ (5.63), while the 5/6 cases were HER2 negative. Based on the 2018 ASCO/CAP guidelines overall, 2/26 CDC cases (8%) were HER2+. The present study provides evidence for testing, in future studies, HER2 to assess its clinical value as a novel target for the treatment of this highly malignant cancer.
Highlights
Collecting duct carcinoma (CDC) of the kidney, known as Bellini duct carcinoma, is a rare and aggressive variant histology of renal cell carcinoma (RCC), accounting for 1–2% of all RCC [1].Early-stage CDC usually undergo radical nephrectomy with curative intent, whereas chemotherapy alone or in combination with radiation therapy in the adjuvant setting is not recommended [2].at the time of the diagnosis, about half of the cases have already developed metastasis at lymph nodes, bone, lung, liver, and adrenal glands [3,4]
This study aims to provide preliminary evidence that can guide future clinical studies to explore human epidermal receptor-2 (HER2)-targeting drugs in renal collecting duct carcinoma
Considering together IHC and fluorescence in-situ hybridization (FISH) results, we found that 2/26 cases (8%) were HER2 positive (Table 2)
Summary
Early-stage CDC usually undergo radical nephrectomy with curative intent, whereas chemotherapy alone or in combination with radiation therapy in the adjuvant setting is not recommended [2]. At the time of the diagnosis, about half of the cases have already developed metastasis at lymph nodes, bone, lung, liver, and adrenal glands [3,4]. In these metastatic patients (mCDC), the median overall survival (OS) is about 13 months after diagnosis [5]. Gemcitabine plus cisplatin chemotherapy is the only recommended therapy for the first-line treatment of mCDC
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